Pharmacologic vitreolysisFloater-focused internet forums occasionally contain posts citing the potential for up-and-coming drugs to cure vitreous opacities through pharmacologic, rather than surgical treatment. To date, none of the substances cited have been designed specifically for this purpose; rather, they are intended to treat other vitreoretinal conditions such as diabetic retinopathy and macular holes. This area of medicine utilises pharmaceuticals to manipulate the gel state of the vitreous and its attachment to the retina. This is referred to as pharmacologic vitreolysis.

The earliest efforts in this field utilised enzymes to effect changes to the vitreous hence the term enzymatic vitreolysis was coined.  More recently, the term pharmacologic vitreolysis has supplanted the original term enzymatic vitreolysis to include some non-enzyme substances. Although these substances were not intended to treat vitreous opacities, their mechanisms of action may have an effect on the appearance of floaters.

Phamacologic agents may be classified by their biological activity, that is, whether they induce liquefaction of the vitreous (liquefactant) or vitreous separation from the retina (interfactant). Both actions are necessary to avoid complications. Several of the substances of interest are summarized here. Notice that some are categorized as both liquefactant and interfactant.

Pharmacologic vitreolysis classification based on biologic activity:

Pharmacologic vitreolysis classification based on biologic activity

* non-enzymatic agents
tPA – tissue plasminogen activator
Note: tPA, plasmin, microplasmin, nattokinase, and vitreosolve are believed to be both liquefactants and interfactants.

From Sebag J., Retina 29:871-4, 2009. With permission.

Among these, several have garnered particular interest:

Nattokinase (NAT subtilisin)

Classification: liquefactant, interfactant

Nattokinase is an enzyme with a strong fibrinolytic effect (i.e., dissolves fibrin).  It was originally derived from natto which is a popular soybean cheese in Japan. Nattokinase is now under investigation for prevention of cardiovascular thrombotic events and reducing blood pressure. Research performed by Takano, et al. demonstrated that Nattokinase could produce a complete posterior vitreous detachment but more research is needed to clarify the safety and efficacy aspects of Nattokinase as a vitreolytic agent.

Microplasmin

Classification: liquefactant, interfactant

Plasmin is an enzyme in blood responsible for dissolving blood plasma proteins, specifically, fibrin clots. Microplasmin is a truncated and stable form of this enzyme http://www.thrombogenics.com/html/pipeline2.asp accessed June, 2010. ThromboGenics is facilitating Microplasmin (aka Ocriplasmin) research. which will assess its ability to effect a posterior vitreous detachment. To date, clinical trials have been positive and Microplasmin has completed phase III trials for its application to relieve vitreomacular adhesion. It is unclear whether microplasmin will have any effect on ‘floaters’. There is reason to be concerned that it might even increase ‘floaters’ although research subjects have not complained about this during clinical trials.

Chondroitinase

Classification: liquefactant, interfactant

Chondroitinase completed phase I trials in the U.S. several years ago. To date, the results have not been published and phase II trials have not begun. Regardless, its ability to effect both the vitreous and vitreo-retinal adhesion have generated interest in the use of this agent to aid in surgery. Initial work was performed by Drs. Greg Hageman and Steve Russel. In subsequent years, Storz / Bausch and Lomb has obtained the license to research this agent.

Vitreosolve

Classification: liquefactant, interfactant

Vitreosolve is a urea derived molecule originally developed by VitreoRetinal Technologies Inc. for the treatment of diabetic retinopathy (DR). Similar to other DR treatments, Vitreosolve is intended to induce posterior vitreous detachment and vitreous liquefaction. Interestingly, patients who were treated in early clinical trials reported, “either a reduction or elimination of floaters”4. Unfortunately, development of Vitreosolve stalled when Phase III clinical trials encountered problems and VitreoRetinal Technologies Inc. turned its assets over to creditors. Numoda Capital Innovations recently acquired Vitreosolve with the intention of continuing its development under the management of Innovations in Sight.

References

  1. Bishop, P N, D McLeod, and A Reardon. “Effects of Hyaluronan Lyase, Hyaluronidase, and Chondroitin ABC Lyase on Mammalian Vitreous Gel.” Investigative ophthalmology & visual science 40 (1999): 2173–8. Print.
  2. Gandorfer, Arnd et al. “Posterior Vitreous Detachment Induced by Microplasmin.” Investigative ophthalmology & visual science 45 (2004): 641–7. Print.
  3. Hageman, G.S., and S.R. Russell. “Chondroitinase-Mediated Disinsertion of the Primate Vitreous Body.” Investigative Ophthalmology & Visual Science 35 (1994): 1260. Print.
  4. Paul Karpecki, and Diana Shechtman. “A New Drug to Combat PDR.” Review of Optometry 145.11 (2008): n. pag. Web. 8 Aug. 2012.
  5. Sebag, J. “Pharmacologic Vitreolysis–premise and Promise of the First Decade.” Retina (Philadelphia, Pa.) 29 (2009): 871–4. Print.
  6. de Smet, Marc D et al. “Microplasmin: Ex Vivo Characterization of Its Activity in Porcine Vitreous.” Investigative ophthalmology & visual science 50 (2009): 814–9. Print.
  7. Takano, Akiomi et al. “Posterior Vitreous Detachment Induced by Nattokinase (subtilisin NAT): a Novel Enzyme for Pharmacologic Vitreolysis.” Investigative ophthalmology & visual science 47 (2006): 2075–9. Print.